Nicorandil antiallodynic activity in a model of neuropathic pain is associated with the activation of ATP-dependent potassium channels and opioidergic pathways, and reduced production of cytokines and neutrophils recruitment in paw, sciatic nerve, and dorsal root ganglia

• Published in: Pharmacological reports 2024-10, Vol.76 (5), p.1067-1078
• Main Authors: Braga, Alysson V., Morais, Marcela Í., Delfino, Darly G. S., Costa, Sarah O. A. M., Barbosa, Bárbara C. M., Rodrigues, Felipe F., Melo, Ivo S. F., Matos, Rafael C., Castro, Brenda F. M., Cunha Júnior, Armando S., Braga, Taniris C., de Fátima, Ângelo, Coelho, Márcio M., Machado, Renes R.
• Format: Article
• Language: English
• Subjects: Analgesics - pharmacology; Animals; Cytokines - metabolism; Disease Models, Animal; Drug Safety and Pharmacovigilance; Ganglia, Spinal - drug effects; Ganglia, Spinal - metabolism; Glyburide - pharmacology; Hyperalgesia - drug therapy; Hyperalgesia - metabolism; KATP Channels - metabolism; Male; Medicine; Mice; Naltrexone - analogs & derivatives; Naltrexone - pharmacology; Neuralgia - drug therapy; Neuralgia - metabolism; Neutrophil Infiltration - drug effects; Nicorandil - pharmacology; Peroxidase - metabolism; Pharmacotherapy; Pharmacy; Sciatic Nerve - drug effects; Sciatic Nerve - metabolism
• ISSN: 1734-1140; 2299-5684; 2299-5684
• DOI: 10.1007/s43440-024-00640-2

Background Recently, we demonstrated that nicorandil inhibits mechanical allodynia induced by paclitaxel. In the present study, we evaluated the effect induced by nicorandil in a model of neuropathic pain induced by chronic constriction injury (CCI) in mice. We also investigated putative mechanisms underlying such an effect. Methods CCI was induced by three ligatures of the left sciatic nerve. Mechanical allodynia was evaluated by measuring the paw withdrawal threshold with an electronic von Frey apparatus. Concentrations of cytokines and myeloperoxidase activity were determined in the paw tissue, sciatic nerve, and dorsal root ganglia (DRG). Results Oral administration of two doses of nicorandil (150 mg/kg po ), but not equimolar doses of nicotinamide or nicotinic acid, attenuated mechanical allodynia induced by CCI. Nicorandil activity was reduced by previous administration of glibenclamide (40 mg/kg) or naltrexone (5 mg/kg or 10 mg/kg). Two doses of nicorandil (150 mg/kg, po ) reduced tumor necrosis factor-α, interleukin-1β and interleukin-6, but not CXCL-1, concentrations in the paw tissue of CCI mice. Two doses of nicorandil (150 mg/kg, po ) reduced concentrations of all these mediators in the sciatic nerve and DRG. Two doses of nicorandil (150 mg/kg, po ) also reduced the myeloperoxidase activity in the paw tissue, sciatic nerve, and DRG. Conclusions Nicorandil exhibits antiallodynic activity in a model of neuropathic pain induced by CCI. Inhibition of cytokines production and reduction of neutrophils recruitment in paw tissue, sciatic nerve, and DRG as well as activation of ATP-dependent potassium channels and opioidergic pathways, underlie nicorandil antiallodynic activity.